In U.S. Pat. Nos. 4,950,224, 5,152,743, 5,151,082, 5,735,809, 5,968,004 and 5,980,478 there are disclosed methods and apparatus for carrying out in-vivo plasmapheresis for separating plasma from other blood components within the body and blood vessels of the patient. Blood plasma and/or selected plasma components separated from whole blood in-vivo by hollow fiber membranes is pumped from the patient via a catheter placed in the superior vena cava to a treatment means such as a dialyzer apparatus, adsorption column, or selective separation apparatus in which toxic metabolic waste products, specific proteins, or other elements in the plasma are removed or treated. After the plasma is treated for removal or recomposition of waste products, water or excess fluids, toxins, and/or deleterious plasma proteins, the treated plasma is returned and reintroduced to the patients' blood stream. The methods and apparatus described in the aforesaid patents are incorporated herein by reference. In U.S. Pat. Nos. 6,607,501, and 6,632,192 these membranes and catheter systems are utilized for providing metabolic support for tissue engineering devices and systems as well as for the selective reduction of segmental intracellular and extracellular edema.
Methods of plasma and toxin removal from blood as taught by the above patents are unique and substantially superior to conventional means of hemodialysis as presently practiced for both acute and chronic kidney failure as well as for therapeutic apheresis applications, primarily because removal of whole blood from the patient's vasculature and treatment of the blood ex-vivo is eliminated from the procedure. In conventional hemodialysis procedures hollow fiber membranes are used in the ex-vivo dialysis and hemofilter cartridges for blood purification and in therapeutic apheresis applications and tissue engingeering applications blood is separated ex-vivo by centrifugation. In hemodialysis procedures the blood is routed from the patient and directed through the center lumen of the hollow fibers in the ex-vivo cartridges while dialysate fluid passes over the outside walls of the fibers within the cartridge cavity in counter-flow direction to blood flow whereby blood toxins are diffused through the fiber membrane and/or water is removed by conductive means. Thus, in hemodialysis toxin diffusion and ultrafiltration are from inside the fiber lumen to a compartment outside the fiber walls where the ultrafiltrate and toxin-saturated dialysate are collected for further processing and/or disposal.
Conventional hollow fiber membranes commercially used for present hemodialysis, hemo-ultrafiltration, and dialyzer cartridges fabricated from proprietary and non-proprietary polymer compositions have symmetrical or asymmetrical fiber wall morphology. The cellular structure and porosity of the fiber wall generally is uniform from the inner lumen to the outside membrane surface. In asymmetrical compositions, both morphology and pore structures vary from the inner lumen to the outer surface cartridges. Conventional hollow fibers or filter membranes are unable to successfully perform in-vivo, intravascular plasma separation because these commercial membranes generally have poor structural strength, acceptable in an encapsulated device external to the body but not acceptable for an in-vivo placement for safety reasons. Further the actual filtration surface of these conventional dialysate hollow fiber membrane filters is on or close to the surface of the inner lumen of these membranes and can not perform satisfactorily in a demanding in-vivo environment of relatively high flow rate of blood at the exterior fiber surface where the filtration surface of the subject filters reside and operate at relatively low lumen pressure and high blood flow rates. For example, typical in-vivo blood flow within a vena cava is about 2.5 L per minute, whereas blood flow through typical dialysate filter apparatus is nearly stagnant (2-300 ml/min/7,000 fibers=0.042 ml/m/fiber), e.g., about 0.42 ml per minute per fiber. Also the trans-membrane pressure (TMP) used in the subject membranes is typically about 50 mm Hg or less, as compared to TMP of 100-300 mm Hg as used in conventional extracorporeal dialysate filters.
In U.S. patent application Ser. No. 09/549,131 filed Apr. 13, 2000, (TRANSVI.007A) entitled “Specialized Hollow Fiber Membranes for In-Vivo Plasmapheresis and Ultrafiltration,” there are disclosed elongated hollow microporous fibers having an asymmetrical fiber wall characterized by a lower mass density adjacent to the inner wall surface extending along the interior lumen of the fiber and a higher mass density adjacent to the outer wall surface. Such a fiber wall morphology and pore structure provide unique characteristics necessary for separating blood plasma and/or plasma water in-vivo where continuous extraction of cell-free plasma or ultrafiltered plasma water and its associated toxins is carried out within the blood vessel of a patient, human or animal. While the aforesaid disclosed fibers are orders of magnitude stronger than conventional fibers commonly used in ex-vivo systems, there exists the possibility of accidental breakage of the fibers during fiber or filter construction, or during insertion or implantation of a filter containing the fiber or under conditions of excessive, accidental, violent trauma experienced by a patient. The use of such fibers in a preferred filter device and catheter assembly are disclosed in U.S. patent application Ser. No. 09/981,783, filed Oct. 17, 2001 (TRANSVI.011A), the description thereof which is incorporated herein by reference, and will be further discussed hereinafter. The fibers are installed in the filter device such that each end of a hollow membrane is attached to the filter device with adhesive or suitable bonding material to prevent loss of the fiber from the assembly should the fiber break anywhere along its length. However, in an unlikely event that a fiber could be broken at two places along its length or at both ends and a portion of the fiber freed from attachment to the catheter, it could be carried by the blood to a patient's lungs with a possible deleterious effect.